Utilizing weak pump depletion to stabilize squeezed vacuum states.

We propose and demonstrate a pump-phase locking technique that makes use of weak pump depletion (WPD) - an unavoidable effect that is usually neglected - in a sub-threshold optical parametric oscillator (OPO). We show that the phase difference between seed and pump beam is imprinted on both light fields by the non-linear interaction in the crystal and can be read out without disturbing the squeezed output. In our experimental setup we observe squeezing levels of 1.96 ± 0.01 dB, with an anti-squeezing level of 3.78 ± 0.02 dB (for a 0.55 mW seed beam at 1064 nm and 67.8 mW of pump light at 532 nm). Our new locking technique allows for the first experimental realization of a pump-phase lock by reading out the pre-existing phase information in the pump field. There is no degradation of the detected squeezed states required to implement this scheme.

Adaptive optical phase estimation using time-symmetric quantum smoothing.

Quantum parameter estimation has many applications, from gravitational wave detection to quantum key distribution. The most commonly used technique for this type of estimation is quantum filtering, using only past observations. We present the first experimental demonstration of quantum smoothing, a time-symmetric technique that uses past and future observations, for quantum parameter estimation. We consider both adaptive and nonadaptive quantum smoothing, and show that both are better than their filtered counterparts. For the problem of estimating a stochastically varying phase shift on a coherent beam, our theory predicts that adaptive quantum smoothing (the best scheme) gives an estimate with a mean-square error up to 2sqrt[2] times smaller than nonadaptive filtering (the standard quantum limit). The experimentally measured improvement is 2.24+/-0.14.

Controlled-release tablets from carrageenans: effect of formulation, storage and dissolution factors.

The purpose of this study was to investigate the potential of two carrageenans, iota-carrageenan and lambda-carrageenan for the preparation of controlled-release tablets. Tablets were compressed on a Carver press and the effect of formulation factors, moisture, and storage on the release of theophylline was studied. The effect of sodium chloride in the tablet formulation and a change in the ionic strength of the dissolution media was studied on the release of three model drugs. The release rate increased both with an increase in tablet diameter and increase in drug to carrageenan ratio in the tablets. The two lubricants studied had a negligible effect on the rate of drug release at their commonly used concentrations. Moisture content of carrageenans, storage of tablets at 37 degrees C/75% RH for 3 months, and incorporation of 10% sodium chloride in the tablets did not have any significant effect on the release rate. The change in ionic strength of simulated gastric fluid altered the release rate whereas the ionic strength of simulated intestinal fluid did not have a significant effect on the release rate. Carrageenan tablets were relatively insensitive to small changes in formulation parameters and dissolution conditions.

A comparison of reflectance and transmittance near-infrared spectroscopic techniques in determining drug content in intact tablets.

Drug contents of intact tablets were determined using non-destructive near infrared (NIR) reflectance and transmittance spectroscopic techniques. Tablets were compressed from blends of Avicel PH-101 and 0.5% w/w magnesium stearate with varying concentrations of anhydrous theophylline (0, 1, 2, 5, 10, 20 and 40% w/w). Ten tablets from each drug content batch were randomly selected for spectral analysis. Both reflectance and transmittance NIR spectra were obtained from these intact tablets. Actual drug contents of the tablets were then ascertained using a UV-spectrophotometer at 268 nm. Multiple linear regression (MLR) models at 1116 nm and partial least squares (PLS) calibration models were generated from the second derivative spectral data of the tablets in order to predict drug contents of intact tablets. Both the reflectance and the transmittance techniques were able to predict the drug contents in intact tablets over a wide range. However, a comparison of the results of the study indicated that the lowest percent errors of prediction were provided by the PLS calibration models generated from spectral data obtained using the transmittance technique.

Application of near-infrared spectroscopy for nondestructive analysis of Avicel powders and tablets.

The purpose of this study was to use near-infrared spectroscopy (NIRS) as a nondestructive technique to (a) differentiate three Avicel products (microcrystalline cellulose [MCC] PH-101, PH-102, and PH-200) in powdered form and in compressed tablets with and without 0.5% w/w magnesium stearate as a lubricant; (b) determine the magnesium stearate concentrations in the tablets; and (c) measure hardness of tablets compressed at several compression forces. Diffuse reflectance NIR spectra from Avicel powders and tablets (compression forces ranging from 0.2 to 1.2 tons) were collected and distance scores calculated from the second-derivative spectra were used to distinguish the different Avicel products. A multiple linear regression model was generated to determine magnesium stearate concentrations (from 0.25 to 2% w/w), and partial least squares (PLS) models were generated to predict hardness of tablets. The NIRS technique could distinguish between the three different Avicel products, irrespective of lubricant concentration, in both the powdered form and in the compressed tablets because of the differences in the particle size of the Avicel products. The percent error for predicting the lubricant concentration of tablets ranged from 0.2 to 10% w/w. The maximum percent error of prediction of hardness of tablets compressed at the various compression forces was 8.8% for MCC PH-101, 5.3% for MCC PH-102, and 4.6% for MCC PH-200. The NIRS nondestructive technique can be used to predict the Avicel type in both powdered and tablet forms as well as to predict the lubricant concentration and hardness.

Controlled-release tablet matrices from carrageenans: compression and dissolution studies.

This study investigates the potential of two commercial carrageenans, Gelcarin GP-379 (iota-carrageenan) and Viscarin GP-209 (lambda-carrageenan) to be used for the preparation of controlled-release tablet matrices. Tablets were compressed on an instrumented Stokes single punch machine and compression characteristics of the carrageenans were analyzed. Heckel plots using out-of-die tablet densities were linear with calculated yield pressures of 81.3 MPa and 105.2 MPa for iota- and lambda-carrageenan, respectively. Drug release from tablet formulations that contained equal amounts of the two carrageenans had near zero-order release profiles. There was little or no effect of tablet compression pressure on the drug release profiles from 70 to 175 MPa. As drug loading was increased from 5 to 20%, the diffusional exponent decreased from 1.056 to 0.678. Thirty percent drug loading resulted in breakup of tablets during dissolution and departure from zero-order release. Multiple regression analysis was used to predict the time for 50% release as a function of the concentration of the two carrageenans and a third filler material, microcrystalline cellulose. Predicted values were in good agreement with observed values and R2 for the final cubic model was 0.9984.

Correlation of in vitro and in vivo methodology for evaluation of antacids.

The rate and extent of acid consumption of an antacid suspension and tablet were evaluated by in vitro and in vivo techniques. Four different test procedures were used to estimate in vitro antacid reactivity. In vivo effects were determined in the fasted and postcibal states in normal human subjects by a radiotelemetry procedure. The duration of elevation of intragastric pH greater than 3 was in agreement with in vitro estimates of total acid consumption of the antacid. There was also good correlation between onset, extent, and duration of in vivo antacid activity and a modified in vitro Beekman antacid test procedure. There was no significant difference in antacid activity of the tablet or suspension in either in vitro or in vivo test procedures. A wide variation in antacid activity was observed between subjects and also in the fasted versus postcibal states. These studies emphasize the requirements for standardization of antacid products by comparactive in vitro and in vivo evaluations to facilitate individualized dose titration of the antacid in each patient and correlation of the acid secretion rate in various types of GI disease with the antacid dose.